Matrix Metalloproteinase-9 Relationship With Infarct Growth and Hemorrhagic Transformation in the Era of Thrombectomy

The earliest report I have of MMP-9 being useful for stroke was way back in 2005.  And 15 years later we still have no translational use for it. We keep doing studies but never seem to get anywhere useful with it. A great stroke leader would get something accomplished.

In 2005, the scientist(Mr Gu) had previously played the role of lead author on a study published in the Journal of Neuroscience that had revealed MMP-9 could be a promising area that therapeutic medicines for stroke patients could target.

But while you wait for researchers to actually solve stroke you can read up on MMP-9. I like the red wine molecule solving Alzheimer's symptoms. 

• MMP-9 (18)

Matrix Metalloproteinase-9 Relationship With Infarct Growth and Hemorrhagic Transformation in the Era of Thrombectomy

Laura Mechtouff^1,2*, Thomas Bochaton^2,3, Alexandre Paccalet², Claire Crola Da Silva², Marielle Buisson⁴, Camille Amaz⁴, Morgane Bouin⁵, Laurent Derex¹, Elodie Ong^1,2, Yves Berthezene^6,7, Omer Faruk Eker⁶, Nathalie Dufay⁸, Nathan Mewton⁴, Michel Ovize^2,4, Norbert Nighoghossian^1,2 and Tae-Hee Cho^1,2

• ¹Stroke Department, Pierre Wertheimer Hospital, Hospices Civils de Lyon, Bron, France
• ²CarMeN, INSERM U.1060/Université Lyon1/INRA U. 1397/INSA Lyon/Hospices Civils Lyon, Université de Lyon, Lyon, France
• ³Cardiac Intensive Care Unit, Louis Pradel Hospital, Hospices Civils de Lyon, Bron, France
• ⁴Clinical Investigation Center, INSERM 1407, Louis Pradel Hospital, Hospices Civils de Lyon, Bron, France
• ⁵Cellule Recherche Imagerie, Louis Pradel Hospital, Hospices Civils de Lyon, Bron, France
• ⁶Neuroradiology Department, Pierre Wertheimer Hospital, Hospices Civils de Lyon, Bron, France
• ⁷CREATIS, CNRS UMR 5220, INSERM U1044, University Lyon 1, Lyon, France
• ⁸NeuroBioTec, CRB, Pierre Wertheimer Hospital, Hospices Civils de Lyon, Bron, France

Objective: To assess the relationship between matrix metalloproteinase 9 (MMP-9), a proteolytic enzyme involved in the breakdown of the blood-brain barrier, and infarct growth and hemorrhagic transformation in acute ischemic stroke (AIS) with large vessel occlusion (LVO) in the era of mechanical thrombectomy (MT) using the kinetics of MMP-9 and sequential magnetic resonance imaging (MRI).

Methods: HIBISCUS-STROKE is a cohort study including AIS patients with LVO treated with MT following admission MRI. Patients underwent sequential assessment of MMP-9, follow-up CT at day 1, and MRI at day 6. The CT scan at day 1 classified any hemorrhagic transformation according to the European Co-operative Acute Stroke Study-II (ECASS II) classification. Infarct growth was defined as the difference between final Fluid-Attenuated Inversion Recovery volume and baseline diffusion-weighted imaging volume. Conditional logistic regression analyses were adjusted for main confounding variables including reperfusion status.

Results: One hundred and forty-eight patients represent the study population. A high MMP-9 level at 6 h from admission (H6) (p = 0.02), a high glucose level (p = 0.01), a high temperature (p = 0.04), and lack of reperfusion (p = 0.02) were associated with infarct growth. A high MMP-9 level at H6 (p = 0.03), a high glucose level (p = 0.03) and a long delay from symptom onset to groin puncture (p = 0.01) were associated with hemorrhagic transformation.

Conclusions: In this MT cohort study, MMP-9 level at H6 predicts infarct growth and hemorrhagic transformation.(But what the fuck is the solution to this problem?)

Introduction

Ischemia-reperfusion injury in stroke is defined as a biochemical cascade causing a deterioration of ischemic brain tissue that parallels and antagonizes the beneficial effect of reperfusion (1). A key feature of this process is the proteolytic breakdown of the blood-brain barrier (BBB) vasculature. The increase of BBB permeability is mediated by activation of matrix metalloproteinase (MMP), and especially MMP-9 (2, 3).

So far, the importance of MMP-9 on infarct growth and risk of hemorrhagic transformation has not been explored in relation to mechanical thrombectomy (MT). In the context of intravenous (IV) thrombolysis, early increase of MMP-9 expression may promote hemorrhagic transformation but also infarct growth with subsequent influence on neurological disability (4–12). Since restoration of the blood supply following MT might be more abrupt and potentially cause greater BBB damage despite a timely and successful reperfusion, an appropriate assessment of MMP-9 activity in this setting may provide additional insight into reperfusion injury related to MT (13). We sought to determine whether early MMP-9 level is associated with infarct growth and hemorrhagic transformation. For this purpose, a sequential assessment of MMP-9 and ischemic damage using MRI was implemented in the setting of MT.